The association of attempted suicide with genetic variants in the SLC6A4 and TPH genes depends on the definition of suicidal behavior: a systematic review and meta-analysis.

Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101562664 Publication Model: Electronic Cited Medium: Internet ISSN: 2158-3188 (Electronic) Linking ISSN: 21583188 NLM ISO Abbreviation: Transl Psychiatry Subsets: MEDLINE

Original Publication: New York, NY : Nature Pub. Group

Suicidal Ideation* ; Suicide, Attempted*; Polymorphism, Genetic/*genetics ; Serotonin Plasma Membrane Transport Proteins/*genetics ; Tryptophan Hydroxylase/*genetics; Genetic Predisposition to Disease/genetics ; Humans ; Odds Ratio

The global prevalence of suicide has increased substantially over the last four decades. Suicidal behavior manifests owing to a combination of biological, behavioral and social factors; however, the etiology of suicidality remains elusive. Even though twin studies have reported a significant heritability of 30-50%, meta-analyses have not highlighted a common genetic variant associated with the spectrum of suicidal behavior. Here, we performed a systematic review of the literature (n = 112) to assess the association between serotonergic and non-serotonergic genetic polymorphisms and suicidal behavior. Using an inverse variance random-effects model, we developed pooled odds ratios for the 10 most commonly studied genetic variants related to suicidal behavior, each with at least five independent studies that met our stringent inclusion criteria. Our pooled results indicate no significant correlation between genetic polymorphisms and overall suicidal behavior. However, subgroups of suicide attempts demonstrated actual significance with the serotonin transporter (SLC6A4) 5HTTLPR (OR = 1.13 (95% confidence interval = 1.05-1.21), P = 0.001) and reached nominal significance with the tryptophan hydroxylase rs1800532 (1.22 (1.05-1.41), P = 0.007) variant. Subgroups of suicidal behavior (completions and attempts) displayed reduced heterogeneity compared with the overall suicidal behavior spectrum. Our findings suggest that the 5HTTLPR and rs1800532 polymorphisms are significantly associated with suicide attempts, but not associated with completed suicides. The high degree of heterogeneity in past studies may be attributed to the lack of a phenotypic distinction between suicidal attempts and completions. Consequently, we have identified an important source of phenotypic heterogeneity that provides a rationale for the current lack of a common genetic variant associated with suicidal behavior.

Control Clin Trials. 1986 Sep;7(3):177-88. (PMID: 3802833)
Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 5;150B(4):599-600. (PMID: 18759323)
Bipolar Disord. 2001 Dec;3(6):335-49. (PMID: 11843783)
Mol Psychiatry. 2012 Apr;17(4):433-44. (PMID: 21423239)
Am J Med Genet. 2002 Jul 8;114(5):533-40. (PMID: 12116191)
World J Biol Psychiatry. 2010 Dec;11(8):956-63. (PMID: 20632842)
Nat Rev Genet. 2012 Jan 18;13(2):135-45. (PMID: 22251874)
Psychiatry Res. 2004 Feb 15;125(2):87-93. (PMID: 15006432)
Forensic Sci Int. 2005 May 28;150(1):85-90. (PMID: 15837012)
Mol Psychiatry. 2006 Mar;11(3):252-60. (PMID: 16402137)
Science. 1996 Nov 29;274(5292):1527-31. (PMID: 8929413)
Biol Psychiatry. 2007 Mar 1;61(5):725-7. (PMID: 17046723)
Psychiatry Res. 2009 Dec 30;170(2-3):204-7. (PMID: 19897250)
J Psychiatr Res. 2003 Sep-Oct;37(5):375-86. (PMID: 12849930)
Lancet. 1983 Jan 29;1(8318):214-6. (PMID: 6130248)
Am J Med Genet. 2002 Apr 8;114(3):340-2. (PMID: 11920860)
Am J Med Genet B Neuropsychiatr Genet. 2009 Mar 5;150B(2):290-4. (PMID: 18521860)
Am J Med Genet. 2000 Feb 7;96(1):56-60. (PMID: 10686553)
Psychiatr Clin North Am. 2008 Jun;31(2):179-203. (PMID: 18439443)
Psychiatr Genet. 1999 Jun;9(2):97-100. (PMID: 10412189)
Science. 1982 Jun 18;216(4552):1337-9. (PMID: 7079769)
QJM. 2011 May;104(5):455-8. (PMID: 21051476)
Int J Neuropsychopharmacol. 2012 Sep;15(8):1037-42. (PMID: 21875455)
J Affect Disord. 2001 Sep;66(1):71-4. (PMID: 11532534)
JAMA. 2000 Apr 19;283(15):2008-12. (PMID: 10789670)
Ann N Y Acad Sci. 1997 Dec 29;836:1-11. (PMID: 9616791)
Pharmacogenetics. 1997 Aug;7(4):271-81. (PMID: 9295055)
Am J Med Genet B Neuropsychiatr Genet. 2005 Jan 5;132B(1):46-9. (PMID: 15389757)
Nat Rev Neurosci. 2003 Oct;4(10):819-28. (PMID: 14523381)
Wien Klin Wochenschr. 2007;119(15-16):463-75. (PMID: 17721766)
Stat Med. 2002 Jan 15;21(1):35-50. (PMID: 11782049)
Arch Gen Psychiatry. 1998 Jan;55(1):33-7. (PMID: 9435758)
Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):617-22. (PMID: 18174335)
Experientia. 1988 Feb 15;44(2):127-30. (PMID: 2964377)
Mol Psychiatry. 2001 Mar;6(2):127-8. (PMID: 11317212)
Hum Genet. 2006 Apr;119(3):233-40. (PMID: 16450114)

0 (SLC6A4 protein, human)
0 (Serotonin Plasma Membrane Transport Proteins)
EC 1.14.16.4 (Tryptophan Hydroxylase)

Date Created: 20121004 Date Completed: 20130314 Latest Revision: 20211021

20231215

PMC3565826

10.1038/tp.2012.96

23032942